The Ribosomal Gene Loci-The Power behind the Throne

doi:10.3390/genes12050763

Review

. 2021 May 18;12(5):763.

doi: 10.3390/genes12050763.

The Ribosomal Gene Loci-The Power behind the Throne

Konstantin I Panov^{1

2}, Katherine Hannan^{2

3}, Ross D Hannan^{2

3

4

5

6}, Nadine Hein²

Affiliations

¹ PGJCCR and School of Biological Sciences, Queen's University, Belfast BT9 5DL, UK.
² ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Acton 2601, Australia.
³ Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville 3010, Australia.
⁴ Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
⁵ Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia.
⁶ School of Biomedical Sciences, University of Queensland, St Lucia 4067, Australia.

PMID: 34069807
PMCID: PMC8157237
DOI: 10.3390/genes12050763

Review

The Ribosomal Gene Loci-The Power behind the Throne

Konstantin I Panov et al. Genes (Basel). 2021.

. 2021 May 18;12(5):763.

doi: 10.3390/genes12050763.

Authors

Konstantin I Panov^{1

2}, Katherine Hannan^{2

3}, Ross D Hannan^{2

3

4

5

6}, Nadine Hein²

Affiliations

¹ PGJCCR and School of Biological Sciences, Queen's University, Belfast BT9 5DL, UK.
² ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Acton 2601, Australia.
³ Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville 3010, Australia.
⁴ Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
⁵ Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia.
⁶ School of Biomedical Sciences, University of Queensland, St Lucia 4067, Australia.

PMID: 34069807
PMCID: PMC8157237
DOI: 10.3390/genes12050763

Abstract

Nucleoli form around actively transcribed ribosomal RNA (rRNA) genes (rDNA), and the morphology and location of nucleolus-associated genomic domains (NADs) are linked to the RNA Polymerase I (Pol I) transcription status. The number of rDNA repeats (and the proportion of actively transcribed rRNA genes) is variable between cell types, individuals and disease state. Substantial changes in nucleolar morphology and size accompanied by concomitant changes in the Pol I transcription rate have long been documented during normal cell cycle progression, development and malignant transformation. This demonstrates how dynamic the nucleolar structure can be. Here, we will discuss how the structure of the rDNA loci, the nucleolus and the rate of Pol I transcription are important for dynamic regulation of global gene expression and genome stability, e.g., through the modulation of long-range genomic interactions with the suppressive NAD environment. These observations support an emerging paradigm whereby the rDNA repeats and the nucleolus play a key regulatory role in cellular homeostasis during normal development as well as disease, independent of their role in determining ribosome capacity and cellular growth rates.

Keywords: RNA polymerase I; cancer; cell fate; differentiation; genome architecture; heterochromatin; nucleolar associated domain (NAD); nucleolus; ribosomal genes; transcription.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
rDNA gene arrays (purple) are located on the short arms of the human acrocentric chromosomes. Organization of a single rDNA gene: enhancer, upstream control element (UCE), core promoter (CORE), 5′/3′ external transcribed spacer (ETS), 18S, 5.8S, 28S, internal transcribed spacer (ITS1/2), and transcription terminator factor 1 (TTF-1) site.

**Figure 2**
Proposed model of dynamically regulated long-range rDNA–NAD interactions during malignant transformation and their impact on Pol II-dependent transcription at associated loci. Lamina-associated domain (LAD); nucleolus associated domain (NAD); red: transcriptionally repressed Pol II-dependent genes; blue: actively transcribed Pol II-dependent genes.

See this image and copyright information in PMC

Cited by

The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis.
McCool MA, Bryant CJ, Abriola L, Surovtseva YV, Baserga SJ. McCool MA, et al. PLoS Biol. 2024 Jul 8;22(7):e3002718. doi: 10.1371/journal.pbio.3002718. eCollection 2024 Jul. PLoS Biol. 2024. PMID: 38976757 Free PMC article.
Role of Amino Acid Arginine and Nitric Oxide in Mechanisms of Cytoprotective Effect of Non-Opiate Leu-Enkephalin Analogue In Vitro.
Sazonova EN, Lebed'ko OA, Pinaeva OG, Tsimbalist NA, Kupriyanova DA, Tarasov PK, Malofey YB. Sazonova EN, et al. Bull Exp Biol Med. 2021 Dec;172(2):270-275. doi: 10.1007/s10517-021-05374-2. Epub 2021 Dec 2. Bull Exp Biol Med. 2021. PMID: 34855076 Free PMC article.
R-Loops in Genome Instability and Cancer.
Li F, Zafar A, Luo L, Denning AM, Gu J, Bennett A, Yuan F, Zhang Y. Li F, et al. Cancers (Basel). 2023 Oct 14;15(20):4986. doi: 10.3390/cancers15204986. Cancers (Basel). 2023. PMID: 37894353 Free PMC article. Review.
A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis.
Martin ET, Blatt P, Nguyen E, Lahr R, Selvam S, Yoon HAM, Pocchiari T, Emtenani S, Siekhaus DE, Berman A, Fuchs G, Rangan P. Martin ET, et al. Dev Cell. 2022 Apr 11;57(7):883-900.e10. doi: 10.1016/j.devcel.2022.03.005. Dev Cell. 2022. PMID: 35413237 Free PMC article.
A high-throughput assay for directly monitoring nucleolar rRNA biogenesis.
Bryant CJ, McCool MA, Abriola L, Surovtseva YV, Baserga SJ. Bryant CJ, et al. Open Biol. 2022 Jan;12(1):210305. doi: 10.1098/rsob.210305. Epub 2022 Jan 26. Open Biol. 2022. PMID: 35078352 Free PMC article.

See all "Cited by" articles

References

1. Miller O.L., Jr., Beatty B.R. Visualization of nucleolar genes. Science. 1969;164:955–957. doi: 10.1126/science.164.3882.955. - DOI - PubMed
1. Birch J.L., Zomerdijk J.C. Structure and function of ribosomal RNA gene chromatin. Biochem. Soc. Trans. 2008;36:619–624. doi: 10.1042/BST0360619. - DOI - PMC - PubMed
1. Merz K., Hondele M., Goetze H., Gmelch K., Stoeckl U., Griesenbeck J. Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules. Genes Dev. 2008;22:1190–1204. doi: 10.1101/gad.466908. - DOI - PMC - PubMed
1. Marechal V., Elenbaas B., Piette J., Nicolas J.C., Levine A.J. The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol. Cell Biol. 1994;14:7414–7420. doi: 10.1128/MCB.14.11.7414. - DOI - PMC - PubMed
1. Lohrum M.A., Ludwig R.L., Kubbutat M.H., Hanlon M., Vousden K.H. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell. 2003;3:577–587. doi: 10.1016/S1535-6108(03)00134-X. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources

[1] Miller O.L., Jr., Beatty B.R. Visualization of nucleolar genes. Science. 1969;164:955–957. doi: 10.1126/science.164.3882.955. - DOI - PubMed

[2] Miller O.L., Jr., Beatty B.R. Visualization of nucleolar genes. Science. 1969;164:955–957. doi: 10.1126/science.164.3882.955. - DOI - PubMed

[3] Birch J.L., Zomerdijk J.C. Structure and function of ribosomal RNA gene chromatin. Biochem. Soc. Trans. 2008;36:619–624. doi: 10.1042/BST0360619. - DOI - PMC - PubMed

[4] Birch J.L., Zomerdijk J.C. Structure and function of ribosomal RNA gene chromatin. Biochem. Soc. Trans. 2008;36:619–624. doi: 10.1042/BST0360619. - DOI - PMC - PubMed

[5] Merz K., Hondele M., Goetze H., Gmelch K., Stoeckl U., Griesenbeck J. Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules. Genes Dev. 2008;22:1190–1204. doi: 10.1101/gad.466908. - DOI - PMC - PubMed

[6] Merz K., Hondele M., Goetze H., Gmelch K., Stoeckl U., Griesenbeck J. Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules. Genes Dev. 2008;22:1190–1204. doi: 10.1101/gad.466908. - DOI - PMC - PubMed

[7] Marechal V., Elenbaas B., Piette J., Nicolas J.C., Levine A.J. The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol. Cell Biol. 1994;14:7414–7420. doi: 10.1128/MCB.14.11.7414. - DOI - PMC - PubMed

[8] Marechal V., Elenbaas B., Piette J., Nicolas J.C., Levine A.J. The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol. Cell Biol. 1994;14:7414–7420. doi: 10.1128/MCB.14.11.7414. - DOI - PMC - PubMed

[9] Lohrum M.A., Ludwig R.L., Kubbutat M.H., Hanlon M., Vousden K.H. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell. 2003;3:577–587. doi: 10.1016/S1535-6108(03)00134-X. - DOI - PubMed

[10] Lohrum M.A., Ludwig R.L., Kubbutat M.H., Hanlon M., Vousden K.H. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell. 2003;3:577–587. doi: 10.1016/S1535-6108(03)00134-X. - DOI - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The Ribosomal Gene Loci-The Power behind the Throne

Affiliations

The Ribosomal Gene Loci-The Power behind the Throne

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Related information

LinkOut - more resources

Full Text Sources